Lecture 24: Genetic disorders

Sickle Cell Disease

• Sickle cell disease is a recessive phenotype that affects millions of people worldwide.
• It causes severe pain from obstructed blood flow.
• Heterozygous individuals (sickle cell trait) have greater resistance to malaria.
• Malaria-infected red blood cells tend to sickle and are removed by macrophages.

Pedigrees

• A pedigree is a family tree indicating the presence or absence of a trait for each member.
• Conventions: for unaffected male, for unaffected female, for affected male, and for affected female.

Huntington's Disease

• Huntington's disease is an autosomal dominant disorder.
• Healthy individuals are homozygous recessive.
• Affected individuals are homozygous dominant or heterozygous.
• The abnormal HTT allele is characterized by additional CAG repeats in the sequence.
• Symptoms manifest between 30-45 years of age.
• Patients may have had children before diagnosis.

Autosomes and Sex Chromosomes

• Autosomes are chromosomes 1-22, which don't determine our sex.
• X and Y chromosomes are the sex chromosomes, which determine our sex.

Sex Determination

• Sex in humans is determined by X and Y chromosomes.
• The sex-determining region on the Y chromosome (SRY gene) is responsible for the initiation of male sex determination.

Sex-Linked Disorders

• X-linked dominant disorders:
  • Affected females can have a homozygous dominant or heterozygous genotype.
  • Affected males are hemizygous (one abnormal allele is sufficient to cause the disorder).
• X-linked recessive disorders:
  • Affected females have a homozygous recessive genotype.
  • Affected males are hemizygous.
• Y-linked disorders:
  • The abnormal allele exists on the Y chromosome and can only be passed from father to son.

Red-Green Colour Blindness

• Red-green colour blindness is an X-linked recessive disorder.
• It results from mutations in the OPN1LW or OPN1MW gene, causing abnormal opsin pigments in cone cells of the retina.
• Affected individuals have trouble distinguishing between some shades of red, yellow, and green.

Haemophilia A and Haemophilia B

• Haemophilia A and Haemophilia B are X-linked recessive disorders.
• They are characterized by clotting deficiencies due to abnormal alleles coding for proteins that cannot participate effectively in blood clotting.
• Haemophilia A is the most common type, with a deficiency of clotting factor VIII.
• Haemophilia B (Christmas disease, Royal disease) has a deficiency of clotting factor IX.

Haemophilia Manifestation in Female Carriers

• Female carriers have a heterozygous genotype and generally have a healthy phenotype.
• Some may have mild symptoms of haemophilia, and severe symptoms are rare but possible.
• X chromosome inactivation (lyonisation) influences the diversity in phenotypes for female carriers.